HMG-CoA reductase inhibitors, commonly known as statins, are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which catalyzes the rate-limiting conversion of HMG-CoA into mevalonate by HMG-CoA reductase during de novo cholesterol biosynthesis. Statins are used primarily to treat hyperlipidemias and are the most effective lipid-lowering drugs currently available. They have also been shown to exhibit pleiotropic effects and may have potential uses in the treatment of other conditions, such as diabetes, depression, cancer, osteoporosis, ventricular arrhythmias, peripheral arterial disease, and idiopathic dilated cardiomyopathy.
Side effects of statins include myopathy (including myalgia), increased risk of diabetes, short-term memory loss, cumulative trauma disorder, and abnormalities in liver enzyme tests. Myopathy is the most common side effect, with symptoms that can include muscle fatigue, weakness, pain, and rhabdomyolysis (i.e., the breakdown of muscle fibers that leads to the release of muscle fiber contents (inter alia, myoglobin) into the bloodstream). Rhabdomyolysis is rare, occurring in ˜0.1% of patients; the occurrence of other myopathic symptoms has been estimated at 1-5% of patients in controlled studies using selected patients with 35% of eligible patients excluded (LaRosa et al., New England Journal of Medicine 2005, 352: 1425-35). An observational study (PRIMO) involving 7924 French unselected outpatients on statin therapy, reported 10.5% of statin users experienced statin-related myalgia/myopathy (Bruckert et al., Cardiovascular Drugs and Therapy 2005, 19: 403-14). Other observational studies have estimated that 9-20% of statin users experience statin-related muscle symptoms. Physical exercise appears to exacerbate the incidence of myalgia, with as many as 25% of statin users who exercise experiencing muscle fatigue, weakness, aches, and cramping.
Thus, there is a need in the art to improve treatment of statin-related diseases and disorders by alleviating said deleterious side effects.